Presentation from the International Congress of the Royal College of Psychiatrists 24-27 June 2014, London

1. Implications for clinicians of the Barker hypothesis
(what can we do about modifiable in utero risk factors?)
Professor Louise M Howard
Section of Women’s Mental Health
Institute of Psychiatry
King’s College London

2. Copyright restrictions may apply.
Grote, N. K. et al. Arch Gen Psychiatry 2010;67:1012-1024.
Effect of Antenatal Depression on Outcomes of PTB, LBW, and IUGR
Mental disorders and adverse fetal outcomes
Risk of LBW associated with antenatal depression sig larger in developing
countries (RR=2.05; 95% confidence interval, 1.43–2.93) compared with US
(RR=1.10; 95% confidence interval, 1.01–1.21) or European social democracies
(RR=1.16; 95% confidence interval, 0.92–1.47).

3. Meta-analysis in 1996 of OCs
Recent evidence from cohort studies:
• pregnancy complications incl gestational hypertension, placental
abruption, pre-eclampsia,
• preterm birth
• small for gestational age infants
• low APGAR scores in infants
Pregnancy and fetal outcomes and psychotic disorders
Page 2
Bennedsen et al BJP 1998; Boden et al BMJ 2012; Jablensky et al Am J Psychiatry 2005; Lee
& Lin J Affect Disord 2010; Sacker et al Psychol Med1996; Vigod et al BJOG 2014

4. Meta-analysis of fetal death/stillbirth rate
in women with psychosis
Webb et al. American Journal of Psychiatry 2005

5. Neonatal deaths: relative risks of mortality for offspring of
mothers admitted with psychiatric illness vs Danish population
King-Hele S et al. Arch Dis Child Fetal Neonatal Ed 2009
Copyright © BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health. All rights reserved.

6. In utero environment associated with mental disorders –
potential risk factors and targets for intervention
• Psychiatric morbidity
• Other modifiable risk factors associated with mental
disorders
o medication
o smoking
o substance misuse
o nutritional deficiencies
o obesity
o domestic violence

7. Pregnancy and mental health
Epidemiological studies - pregnancy generally not protective
Vesga-Lopez et al Arch Gen Psychiatry 20085.

8. Date of download: 6/26/2014
Copyright © 2014 American Medical
Association. All rights reserved.
From: Risks and Predictors of Readmission for a Mental Disorder During the Postpartum Period
Munk-Olsen et al. Arch Gen Psychiatry. 2009;66(2):189-195. doi:10.1001/archgenpsychiatry.2008.528
Relative Risks of First Readmission in Relation to Childbearing Among Danish Womena
Figure Legend:

9. Tertiary clinical sample - 22% with bipolar disorder relapse during pregnancy
Bipolar disorders greater risk than depression
Incidence rate ratio=4.85 (95% CI=3.32–7.23)
Impact of pregnancy on psychosis Page 8
Taylor et al In Prep; Viguera et al Am J Psychiatry 2011
Pregnant women in contact with SLAM
secondary mental health services
(CRIS 2007-11):
190 bipolar disorder – 15% relapsed in
pregnancy
236 non-affective psychosis – 26%
relapsed in pregnancy

10. Kaplan-Meier Survival Functions for Pregnant Patients With Bipolar
Disorder Who Maintained or Discontinued Treatment
Viguera et al, Am J Psychiatry 2007
Mood stabilizer
discontinuation ass with
recurrence of BPD episode
(RR 2) and shorter time to
recurrence (adj HR 2.5)
Abrupt discontinuation vs
gradual discontinuation
(RR=1.4)
Other predictors of relapse
include bipolar II disorder
diagnosis, earlier onset,
more recurrences/year,
recent illness, use of
antidepressants, use of
anticonvulsants versus
lithium
CRIS study will investigate predictors of
relapse for bipolar disorder & schizophrenia

11. Study in community patients in antenatal care did not find antidepressants
reduced risk of depression (adj HR 0.88 [0.51—1.50] (Yonkers et al 2012)
Risk of relapse highest in women with h/o >4 depressive epsiodes
Risk of relapse if discontinue prophylactic medication Page 10
Cohen, L. S. et al. JAMA 2006;295:499-507

12. Impact of medication

13. Valproate – high rate of major malformations (10%), lowers IQ
Psychotropic Medication in pregnancy Page 12
Meador et al N Engl J Med 2009;

14. Smoking and adverse fetal outcomesPage 13
MacCabe et al Bipolar Disorders 2007

15. Mental disorders and smoking in pregnancy
• Leading preventable cause of fetal/infant morbidity & mortality in UK
• Pregnant women with mental disorders are more likely to smoke
• Cochrane SR (72 RCTs; n>25,000): Smoking cessation programmes in
pregnancy reduce the proportion continuing smoke, improve birth outcomes
• Women with mental disorders may be less likely to be supported to stop
smoking, but are likely to need intensive smoking cessation programmes
Nested qualitative study of 27 women – health professionals & women
prioritised mental health over smoking
Some women thought stress may be worse for baby than smoking
“I think there are more harmful things than smoking. Like…..to take some medicaments or
even alcohol”.
Women reported health professionals also prioritised mental health over smoking
“don’t give up…we don’t want you getting anxiety or stressed”
Limited evidence on substance misuse
Howard et al BJOG 2013; Lumley et al 2009

16. One third of US women are overweight (BMI 25-30kg/m2) or obese (BMI >
30 kg/m2) when they become pregnant, with rising prevalence
UK - 16% women were obese at the start of pregnancy in 2004, 9.9% in
1990.
Obesity in pregnancy associated with adverse pregnancy outcomes incl
congenital neurological defects, childhood obesity, childhood ADHD
Systematic reviews:
• obesity associated with all categories of perinatal mental disorders
(50% pregnant women with psychosis on APs - overweight/ obese;
gestational diabetes)
• SMI child-bearing aged women more likely to have low folate and
B12; little research into other nutritional deficiencies
Some studies showing perinatal depression is associated with sub-
optimal diet
Obesity and nutrition Page 15
Barker et al 2013; Kulkarni et al 2014; McColl et al 2013; Molyneaux et al 2014;
Stothard et al JAMA 2009

17. Healthy dietary pattern scores by antenatal
depression status and BMI category (ALSPAC)
Healthydietarypatternscore
Normal weight Overweight Obese
Molyneaux et al In Prep

18. Domestic violence and birth outcomes Page 17
Shah and Shah J Women’s Hlth 2010

19. • Systematic review: high prevalence and increased odds (2-3) of
domestic violence among pregnant women across all diagnoses
studied
• CRIS SLAM data – 19% experienced domestic violence in pregnancy
• Identification of domestic violence by clinicians occurs in 10-30% of
cases
• Cochrane review– preliminary evidence on effectiveness of DV
interventions in pregnancy including advocacy
• Multi-faceted training and linked advocacy programmes effective in
improving identification and referral rates in primary care
• Pilot programme in secondary mental health care reduces abuse and
improves quality of life and social inclusion
• NICE (2014) guidance on identification and care pathways
Domestic violence & perinatal mental disordersPage 18
Feder et al 2011; Howard et al 2010; Howard et al 2013;
Jahanfar et al 2013; Trevillion et al 2013

20. Page 19
Characteristics of pregnant women on antipsychotics:
Australian cohort. Kulkarni et al PlosOne 2014

21. Page 20Whole sample
N = 456
Non-affective
group, N=236
Affective
group, N=220
P*
Deprivation score, median(range)1 34.9 (3.8-77.2) 35.4 (3.8-77.2) 33.6 (6.8-9.7) 0.226
Maternal age at 1st index delivery,
mean(SD),
31.8 (6.2) 30.9 (6.4) 32.9 (5.8) <0.001
Partner during 1st index pregnancy
Yes 294 (71.5) 143 (68.1) 151 (75.1) 0.114
No 117 (28.5) 67 (31.9) 50 (24.9)
History of domestic abuse before
pregnancy
159 (34.9) 83 (35.2) 76 (34.6) 0.889
Domestic abuse in pregnancy 86 (18.9) 45 (19.1) 41 (18.6) 0.906
Smoking in pregnancy 79 (17.3) 51 (21.6) 28 (12.7) 0.012
Alcohol use in pregnancy 77 (16.9) 40 (17.0) 37 (16.8) 0.970
Substance use in pregnancy 61 (13.4) 39 (16.5) 22 (10.0) 0.041
Time since last admission (years)
1 year 104 (53.6) 65 (56.5) 39 (49.4) 0.326
2 years 90 (46.4) 50 (43.5) 40 (50.6)
Highest HoNOS total (range) 12 (0-36) 12 (0-36) 12 (0-28) 0.768
Taylor et al 2014 In Prep
Pregnant women with SMI under SLAM care 2007-11

22. Women with mental disorders are at risk of adverse
pregnancy, and longer term child, outcomes
Targeting of modifiable risk factors - ideally pre-conception
and during pregnancy - including optimal medication,
should improve outcomes for mother and child
Better understanding of how to optimise mental health and
associated physical health risks with tailored
interventions in the perinatal period is needed
Conclusions Page 21

23. Ackowledgements
Susan Bewley
Deborah Bekele
Jill Demilew
Theresa Marteau
Melissa Rowe
Clare Dolman
Ian Jones
Clare Taylor
Rob Stewart
Jack Ogden
Matthew Broadbent
Emma Molyneaux
Lucilla Poston
Gene Feder
Sian Oram
Kylee Trevillion
This presentation presents independent research funded by the National
Institute for Health Research (NIHR). The views expressed in this
publication are those of the author(s) and not necessarily those of the
NHS, the NIHR or the Department of Health.
Contact details:
louise.howard@kcl.ac.uk